Endotoxin Desensitization of Human Mononuclear Cells after Cardiopulmonary Bypass

Abstract

Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

“…In summary, TNF-a synthesis was independently influenced by the time of PBMNC isolation and sera preparation. synthesis of all measured pro-inflammatory cytokines and IL-10 serum levels, IL-10 alone cannot explain the inhibitory activity in patient sera after CPB, neither can monoclonal anti-IL-10 antibodies [15] nor complete absorption of IL-10 abolished TNF-a-inhibitory activity in patient sera after CPB [5]. As IL-10 is not released before aortic unclamping (in our study approximately 60 min.…”

“…Recently it was demonstrated that TNF-a-inhibitory humoral activities are released after CPB [5,15]. Several stress-induced humoral mediators are increased after CPB, e. g. cortisol [16,17], prostaglandins (e. g. PGE 2 ) [18], soluble cytokine receptors [6] and anti-inflammatory cytokines [4].…”

“…Epinephrine and norepinephrine inhibit TNF-a and IL-6 synthesis, while enhancing IL-10 synthesis in LPS stimulated whole blood in vitro and in vivo [27,28]. One could assume that downregulation of pro-inflammatory cytokine synthesis after CPB is a result of stress-induced release or postoperative administration of catecholamines, but labetalol failed to completely restore TNF-a synthesis in whole blood drawn after CPB in vitro [15].…”

Heparin-induced thrombocytopenia: further evidence for a unique immune response

“…After an initial systemic inflammatory response, major surgery (including cardiac surgery) leads to an anti-inflammatory state characterized by transient lymphocytopenia with impairment of T-cell activation and down-regulation of CD14 on monocytes. 15,43,44 When stimulated ex vivo, PBMCs and T lymphocytes obtained from such patients released less IFN-␥, shifting the balance from a Th-1 toward a Th-2 profile. This alteration can be (partially) reversed by the addition of IL-12.…”

Modulation of endotoxin-stimulated TNF-α gene expression by ketamine and propofol in cultured human whole blood

“…Alterations in the number and function of circulating immunocompetent cells have been reported after major surgery, reflecting some degree of "immune depression" [8,9]. Impairment of leukocyte functions essential for host defense, such as the ability to release oxygen free-radicals or to mount a cytokine response to bacterial stimuli, has been shown to correlate with an unfavourable postoperative outcome [5,23].…”